The survival of small cell lung cancer (SCC) patients has recently been improved by more effective chemotherapy. Problems related to the light microscopic classification and recognition of the less well differentiated lung cancers, including SCC, are now more relevant. In addition, new pathologic, kinetic and biochemical alterations have been observed following intensive therapy. This proposal will further explore the relationship of the frequently associated peptide hormone-like product in SCC. Studies in patients, tissue cultures and nude mice with tumor xenografts are designed to increase our understanding of the biology of SCC in relation to the other types of lung cancer. This proposal is designed to provide information that will ensure improved patient management due to better understanding of the clinical, biochemical (metabolic) and pathologic heterogeneity often observed and to developing of an immunocytochemical classification (to aid in the recognition of SCC) and clinically useful biologic markers (to aid in the more accurate assessment of the progression and regression of the neoplasm). Immmunoperoxidase methods, radioimmunoassays, standard suspension cultures, soft agar cultures and tumor xenografts in nude mice will be utilized to study the peptides: ACTH, BMSH, BLPH, BEND, AVP and calcitonin. SCC and non-SCC patients will be serially evaluated before therapy for the presence of the peptide in their tumors (immunoperoxidase method) and in their plasma and other body fluids (radioimmunoassays). The in vitro model (tissue cultures) and the in vivo model (xenografts in nude mice) will be serially established to compare the biochemistry in these models with that in the patients and to further characterize peptide content, location, and secretion.